Neurological complications of pandemic influenza A H1N1 2009 infection: European case series and review

Abstract

Neurological manifestations and outcomes of children with the 2009 H1N1 virus infection have been reported in three American series and from smaller cohorts and case reports worldwide. Of the 83 children admitted between April 2009 and March 2010 with H1N1 virus infection to a tertiary children's hospital in a European setting, five children aged between 2 and 10 years had neurological symptoms. Four patients had seizures and encephalopathy at presentation. One patient presented with ataxia; one developed neuropsychiatric manifestations, and two developed movement disorders during the disease course. Early neuroimaging showed evidence of acute necrotising encephalopathy (ANE) in one case and non-specific white matter changes in another. Initial neuroimaging was normal for the other three, but interval MRI showed increased signal in bilateral periventricular distribution in one and significant cerebral volume loss in the other. Clinical outcomes varied: two recovered fully while three had residual seizures and/or significant cognitive deficits. Conclusion An analysis of our patients along with all reported cases reveal that seizures and encephalopathy were common neurological presentations associated with pandemic 2009 H1N1 influenza virus infection in children requiring hospital admission. Neuroimaging suggestive of ANE, basal ganglia involvement and volume loss appears to be associated with worse neurological outcome.

Neurologic complications of influenza A(H1N1)pdm09

“…We were able to calculate the proportion of neurologic complications in children hospitalized with laboratory-confirmed pandemic influenza in 2009 from 3 studies, 2 in the United States (5.9% and 7.5%) and 1 in the United Kingdom (6.0%). 15,19,29 The proportion of encephalopathy in children hospitalized with laboratory-confirmed pandemic influenza was 1.7% in another study. 12 The presenting symptoms, neurologic complications, CSF and neuroimaging findings, treatment, and outcome of the 87 children are summarized in table e-2.…”

H1N1 Associated Encephalopathy in an Adult: Response to Intravenous Immunoglobulin Supporting an Autoimmune Pathogenesis

“…The criteria stipulate laboratory-confirmed influenza A (H1N1) virus infection associated with seizures, encephalopathy, or encephalitis within 5 days of influenza-like illness (ILI), and without evidence of an alternative etiology [3]. The MRI findings in H1N1 encephalopathy include necrotising encephalopathy, posterior reversible encephalopathy and, as in our patient, callosal lesions typically located in the splenium [1,[5][6][7][8].…”

“…About 6% present with neurological features like seizures, encephalopathy, ataxia, movement disorders and neuropsychiatric manifestations [1]. There are only a few reports of H1N1 involving the nervous system in adults [2,3].…”

Clinical Reasoning: A 57-year-old woman who developed acute amnesia following fever and upper respiratory symptoms

“…Studies of IAE have generally failed to show direct viral infection of the CNS, suggesting an immune-mediated mechanism of tissue injury rather than direct viral toxicity. [1][2][3] Based on these observations and limited case reports of success of immunemodulating therapy in IAE, the patient was treated with a 5-day course of IV methylprednisolone 1000 mg daily as well as 1 mg/kg IV immunoglobulin (IVIg) given over 2 days. She demonstrated some purposeful movements on hospital day 9 and was extubated on hospital day 11.…”

“…3 The most common clinical features of ANE are generalized seizures and alterations of mental status including reduced level of consciousness, abnormal speech, and delirium. 1,3 Radiographic findings include symmetrically distributed lesions of the cerebral white matter and deep structures including the thalami and brainstem, with bilateral necrotic or hemorrhagic thalamic lesions being characteristic. 3,4 Multiple case series of IAE have demonstrated that CSF is generally noninflammatory, and virus can seldom be detected in CSF or in brain tissue.…”